title: Spatiotemporally controlled induction of autophagy-mediated lysosome turnover.
abstract: Lysosomes are the major degradative compartments within cells, harbouring a wide variety of hydrolytic enzymes within their lumen. Release of lysosomal hydrolases from lysosomes into the cell cytoplasm results in cell death. Here we report that damaged lysosomes undergo autophagic turnover. Using a light-induced lysosome impairing scheme that can be controlled spatially and temporally within a cell, we show that damaged lysosomes are selectively ubiquitinated, recruit autophagic proteins and are eventually incorporated into autolysosomes for degradation. We propose that autophagic removal of lysosomes, which we term lysophagy, is a surveillance mechanism that alleviates cells from the adverse effects of lysosomal damage. We envision our method to induce lysosomal damage will enable detailed molecular studies of the lysophagy pathway in the future.
authors.affiliation: Institute of Biological Chemistry, Academia Sinica, Taipei 115, Taiwan.
authors.forename: Yu-Hsien
authors.initials: YH
authors.lastname: Hung
authors.forename: Lily Man-Wen
authors.initials: LM
authors.lastname: Chen
authors.forename: Jin-Yi
authors.initials: JY
authors.lastname: Yang
authors.forename: Wei Yuan
authors.initials: WY
authors.lastname: Yang
mesh_terms: D001343:Autophagy / Q000528:radiation effects; D005453:Fluorescence; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D007211:Indoles / Q000378:metabolism; D008247:Lysosomes / Q000378:metabolism* / Q000528:radiation effects; D009942:Organometallic Compounds / Q000378:metabolism; D062211:Spatio-Temporal Analysis; D013194:Staining and Labeling; D025801:Ubiquitin / Q000378:metabolism; D054875:Ubiquitination / Q000528:radiation effects
chemical_list: D007211:Indoles; D009942:Organometallic Compounds; D025801:Ubiquitin; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; C060570:aluminum phthalocyanine